Cargando…

Novel genomic prognostic biomarkers for dogs with cancer

BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Chon, Esther, Sakthikumar, Sharadha, Tang, Min, Hamilton, Matthew J., Vaughan, Andrew, Smith, Ashley, Sommer, Breann, Robat, Cecilia, Manley, Christina, Mullin, Christine, Ohashi, Emi, Manor, Emily, Custis, James, Intile, Joanne, Shiu, Kai Biu, Parshley, Lisa, Bergman, Noelle, Sheppard‐Olivares, Sabina, Hafeman, Scott, Wright, Zachary, Haworth, David, Hendricks, William, Wang, Guannan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658597/
https://www.ncbi.nlm.nih.gov/pubmed/37801037
http://dx.doi.org/10.1111/jvim.16893
_version_ 1785137453986742272
author Chon, Esther
Sakthikumar, Sharadha
Tang, Min
Hamilton, Matthew J.
Vaughan, Andrew
Smith, Ashley
Sommer, Breann
Robat, Cecilia
Manley, Christina
Mullin, Christine
Ohashi, Emi
Manor, Emily
Custis, James
Intile, Joanne
Shiu, Kai Biu
Parshley, Lisa
Bergman, Noelle
Sheppard‐Olivares, Sabina
Hafeman, Scott
Wright, Zachary
Haworth, David
Hendricks, William
Wang, Guannan
author_facet Chon, Esther
Sakthikumar, Sharadha
Tang, Min
Hamilton, Matthew J.
Vaughan, Andrew
Smith, Ashley
Sommer, Breann
Robat, Cecilia
Manley, Christina
Mullin, Christine
Ohashi, Emi
Manor, Emily
Custis, James
Intile, Joanne
Shiu, Kai Biu
Parshley, Lisa
Bergman, Noelle
Sheppard‐Olivares, Sabina
Hafeman, Scott
Wright, Zachary
Haworth, David
Hendricks, William
Wang, Guannan
author_sort Chon, Esther
collection PubMed
description BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer.
format Online
Article
Text
id pubmed-10658597
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher John Wiley & Sons, Inc.
record_format MEDLINE/PubMed
spelling pubmed-106585972023-10-06 Novel genomic prognostic biomarkers for dogs with cancer Chon, Esther Sakthikumar, Sharadha Tang, Min Hamilton, Matthew J. Vaughan, Andrew Smith, Ashley Sommer, Breann Robat, Cecilia Manley, Christina Mullin, Christine Ohashi, Emi Manor, Emily Custis, James Intile, Joanne Shiu, Kai Biu Parshley, Lisa Bergman, Noelle Sheppard‐Olivares, Sabina Hafeman, Scott Wright, Zachary Haworth, David Hendricks, William Wang, Guannan J Vet Intern Med SMALL ANIMAL BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer. John Wiley & Sons, Inc. 2023-10-06 /pmc/articles/PMC10658597/ /pubmed/37801037 http://dx.doi.org/10.1111/jvim.16893 Text en © 2023 Vidium Animal Health and The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle SMALL ANIMAL
Chon, Esther
Sakthikumar, Sharadha
Tang, Min
Hamilton, Matthew J.
Vaughan, Andrew
Smith, Ashley
Sommer, Breann
Robat, Cecilia
Manley, Christina
Mullin, Christine
Ohashi, Emi
Manor, Emily
Custis, James
Intile, Joanne
Shiu, Kai Biu
Parshley, Lisa
Bergman, Noelle
Sheppard‐Olivares, Sabina
Hafeman, Scott
Wright, Zachary
Haworth, David
Hendricks, William
Wang, Guannan
Novel genomic prognostic biomarkers for dogs with cancer
title Novel genomic prognostic biomarkers for dogs with cancer
title_full Novel genomic prognostic biomarkers for dogs with cancer
title_fullStr Novel genomic prognostic biomarkers for dogs with cancer
title_full_unstemmed Novel genomic prognostic biomarkers for dogs with cancer
title_short Novel genomic prognostic biomarkers for dogs with cancer
title_sort novel genomic prognostic biomarkers for dogs with cancer
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658597/
https://www.ncbi.nlm.nih.gov/pubmed/37801037
http://dx.doi.org/10.1111/jvim.16893
work_keys_str_mv AT chonesther novelgenomicprognosticbiomarkersfordogswithcancer
AT sakthikumarsharadha novelgenomicprognosticbiomarkersfordogswithcancer
AT tangmin novelgenomicprognosticbiomarkersfordogswithcancer
AT hamiltonmatthewj novelgenomicprognosticbiomarkersfordogswithcancer
AT vaughanandrew novelgenomicprognosticbiomarkersfordogswithcancer
AT smithashley novelgenomicprognosticbiomarkersfordogswithcancer
AT sommerbreann novelgenomicprognosticbiomarkersfordogswithcancer
AT robatcecilia novelgenomicprognosticbiomarkersfordogswithcancer
AT manleychristina novelgenomicprognosticbiomarkersfordogswithcancer
AT mullinchristine novelgenomicprognosticbiomarkersfordogswithcancer
AT ohashiemi novelgenomicprognosticbiomarkersfordogswithcancer
AT manoremily novelgenomicprognosticbiomarkersfordogswithcancer
AT custisjames novelgenomicprognosticbiomarkersfordogswithcancer
AT intilejoanne novelgenomicprognosticbiomarkersfordogswithcancer
AT shiukaibiu novelgenomicprognosticbiomarkersfordogswithcancer
AT parshleylisa novelgenomicprognosticbiomarkersfordogswithcancer
AT bergmannoelle novelgenomicprognosticbiomarkersfordogswithcancer
AT sheppardolivaressabina novelgenomicprognosticbiomarkersfordogswithcancer
AT hafemanscott novelgenomicprognosticbiomarkersfordogswithcancer
AT wrightzachary novelgenomicprognosticbiomarkersfordogswithcancer
AT haworthdavid novelgenomicprognosticbiomarkersfordogswithcancer
AT hendrickswilliam novelgenomicprognosticbiomarkersfordogswithcancer
AT wangguannan novelgenomicprognosticbiomarkersfordogswithcancer